Renal Resistive Index: Response to Shock and its Determinants in Critically Ill Patients.

Introduction: Shock is characterized by micro- and macrovascular flow impairment contributing to acute kidney injury (AKI). Routine monitoring of the circulation regards the macrocirculation but not the renal circulation which can be assessed with Doppler ultrasound as renal resistive index (RRI). RRI reflects resistance to flow.

Exercise Training Has Contrasting Effects in Myocardial Infarction and Pressure Overload Due to Divergent Endothelial Nitric Oxide Synthase Regulation.

The beneficial effects of exercise training (EX) on cardiac pathology are well recognized. Previously, we found that the effects of EX on cardiac dysfunction in mice critically depend on the underlying etiology. EX exerted beneficial effects after myocardial infarction (MI); however, cardiac pathology following pressure overload produced by transverse aortic constriction (TAC) was aggravated by EX.

Renal resistive index as an early predictor and discriminator of acute kidney injury in critically ill patients; A prospective observational cohort study.

Background: Acute kidney injury (AKI) complicates shock. Diagnosis is based on rising creatinine, a late phenomenon. Intrarenal vasoconstriction occurs earlier.

Early Prediction of Intensive Care Unit-Acquired Weakness: A Multicenter External Validation Study.

Objectives: An early diagnosis of intensive care unit-acquired weakness (ICU-AW) is often not possible due to impaired consciousness. To avoid a diagnostic delay, we previously developed a prediction model, based on single-center data from 212 patients (development cohort), to predict ICU-AW at 2 days after ICU admission. The objective of this study was to investigate the external validity of the original prediction model in a new, multicenter cohort and, if necessary, to update the model.

Positive End-Expiratory Pressure Ventilation Induces Longitudinal Atrophy in Diaphragm Fibers.

Rationale: Diaphragm weakness in critically ill patients prolongs ventilator dependency and duration of hospital stay and increases mortality and healthcare costs. The mechanisms underlying diaphragm weakness include cross-sectional fiber atrophy and contractile protein dysfunction, but whether additional mechanisms are at play is unknown.

Objectives: To test the hypothesis that mechanical ventilation with positive end-expiratory pressure (PEEP) induces longitudinal atrophy by displacing the diaphragm in the caudal direction and reducing the length of fibers.

Respiratory Viruses in Invasively Ventilated Critically Ill Patients-A Prospective Multicenter Observational Study.

Objectives: The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis.

Design: Prospective observational study.

Setting: Five ICUs in the Netherlands.

Diaphragm Atrophy and Weakness in the Absence of Mitochondrial Dysfunction in the Critically Ill.

Rationale: The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency and increases morbidity, duration of hospital stay, and health care costs. The mechanisms underlying diaphragm weakness are unknown, but might include mitochondrial dysfunction and oxidative stress.

Objectives: We hypothesized that weakness of diaphragm muscle fibers in critically ill patients is accompanied by impaired mitochondrial function and structure, and by increased markers of oxidative stress.

The effects of hyperoxia on microvascular endothelial cell proliferation and production of vaso-active substances.

Background: Hyperoxia, an arterial oxygen pressure of more than 100 mmHg or 13% O, frequently occurs in hospitalized patients due to administration of supplemental oxygen. Increasing evidence suggests that hyperoxia induces vasoconstriction in the systemic (micro)circulation, potentially affecting organ perfusion. This study addresses effects of hyperoxia on viability, proliferative capacity, and on pathways affecting vascular tone in cultured human microvascular endothelial cells (hMVEC).

Relationship between tissue perfusion and coagulopathy in traumatic brain injury.

Background: Traumatic brain injury (TBI)-related coagulopathy appears to be most prevalent in patients with tissue hypoperfusion, but evidence for this association is scarce. This study investigated the relationship between tissue perfusion and hemostatic derangements in TBI patients.

Materials And Methods: Coagulation parameters were measured on emergency department admission in patients with TBI (head abbreviated injury scale ≥ 3).

Moderate hyperoxic versus near-physiological oxygen targets during and after coronary artery bypass surgery: a randomised controlled trial.

Background: The safety of perioperative hyperoxia is currently unclear. Previous studies in patients undergoing coronary artery bypass surgery suggest reduced myocardial damage when avoiding extreme perioperative hyperoxia (>400 mmHg). In this study we investigated whether an oxygenation strategy from moderate hyperoxia to a near-physiological oxygen tension reduces myocardial damage and improves haemodynamics, organ dysfunction and oxidative stress.

Tissue-Specific Suppression of Thyroid Hormone Signaling in Various Mouse Models of Aging.

DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH) is a key regulator of metabolism, changes in TH signaling have widespread effects.

Using Nursing Activities Score to Assess Nursing Workload on a Medium Care Unit.

Background: The medium care unit (MCU) or "stepdown" unit is an increasingly important, but understudied care environment. With an aging population and more patients with complex multiple diseases, many patients often require a higher level of inpatient care even when full intensive care is not indicated. However, the nurse-to-patient ratio required on a MCU is neither well defined nor clear whether this ratio should be adjusted per shift.

Low Cerebral Oxygenation Levels during Resuscitation in Out-of-hospital Cardiac Arrest Are Associated with Hyperfibrinolysis.

Background: The authors investigated whether patients with out-of-hospital cardiac arrest with an initial low cerebral oxygen level during cardiopulmonary resuscitation are more prone to develop hyperfibrinolysis than patients with normal cerebral oxygenation levels and which part of the fibrinolytic system is involved in this response.

Methods: In 46 patients, hyperfibrinolysis was diagnosed immediately upon emergency department admission using rotational thromboelastometry and defined as a lysis more than 15%. Simultaneously, initial cerebral tissue oxygenation was measured using near-infrared spectroscopy, and oxygen desaturation was defined as a tissue oxygenation index (TOI) of 50% or less.

NT-proBNP in cardiopulmonary resuscitated patients treated with mild therapeutic hypothermia is not independently associated with mortality: a retrospective observational study.

Background: In spite of the introduction of mild therapeutic hypothermia (MTH), mortality rates remain high in patients with return of spontaneous circulation (ROSC) after cardiac arrest (CA). To date, no accurate and independent biomarker to predict survival in these patients exists. B-type natriuretic peptide (BNP) was found to provide both prognostic and diagnostic value in various cardiovascular diseases, including survival to hospital discharge in patients with ROSC.

Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients.

Rationale: The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency, and increases morbidity and duration of hospital stay. To date, the nature of diaphragm weakness and its underlying pathophysiologic mechanisms are poorly understood.

Objectives: We hypothesized that diaphragm muscle fibers of mechanically ventilated critically ill patients display atrophy and contractile weakness, and that the ubiquitin-proteasome pathway is activated in the diaphragm.

Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency.

As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg-/- mouse model which -in a C57BL6/FVB F1 hybrid genetic background- displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4-5 months.

Vitamin C revisited.

This narrative review summarizes the role of vitamin C in mitigating oxidative injury-induced microcirculatory impairment and associated organ failure in ischemia/reperfusion or sepsis. Preclinical studies show that high-dose vitamin C can prevent or restore microcirculatory flow impairment by inhibiting activation of nicotinamide adenine dinucleotide phosphate-oxidase and inducible nitric oxide synthase, augmenting tetrahydrobiopterin, preventing uncoupling of oxidative phosphorylation, and decreasing the formation of superoxide and peroxynitrite, and by directly scavenging superoxide. Vitamin C can additionally restore vascular responsiveness to vasoconstrictors, preserve endothelial barrier by maintaining cyclic guanylate phosphatase and occludin phosphorylation and preventing apoptosis.

Priming of microglia in a DNA-repair deficient model of accelerated aging.

Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of microglia is enhanced sensitivity to inflammatory stimuli, referred to as priming.

Exercise training in adverse cardiac remodeling.

Cardiac remodeling in response to a myocardial infarction or chronic pressure-overload is an independent risk factor for the development of heart failure. In contrast, cardiac remodeling produced by regular physical exercise is associated with a decreased risk for heart failure. There is evidence that exercise training has a beneficial effect on disease progression and survival in patients with cardiac remodeling and dysfunction, but concern has also been expressed that exercise training may aggravate pathological remodeling and dysfunction.

Automated peritoneal lavage: an extremely rapid and safe way to induce hypothermia in post-resuscitation patients.

Introduction: Mild therapeutic hypothermia (MTH) is a worldwide used therapy to improve neurological outcome in patients successfully resuscitated after cardiac arrest (CA). Preclinical data suggest that timing and speed of induction are related to reduction of secondary brain damage and improved outcome.

Methods: Aiming at a rapid induction and stable maintenance phase, MTH induced via continuous peritoneal lavage (PL) using the Velomedix Inc.

Spatio-temporal analysis of molecular determinants of neuronal degeneration in the aging mouse cerebellum.

The accumulation of cellular damage, including DNA damage, is hypothesized to contribute to aging-related neurodegenerative changes. DNA excision repair cross-complementing group 1 (Ercc1) knock-out mice represent an accepted model of neuronal aging, showing gradual neurodegenerative changes, including loss of synaptic contacts and cell body shrinkage. Here, we used the Purkinje cell-specific Ercc1 DNA-repair knock-out mouse model to study aging in the mouse cerebellum.